TY - JOUR
T1 - Mice lacking methyl-CpG binding protein 1 have deficits in adult neurogenesis and hippocampal function
AU - Zhao, Xinyu
AU - Ueba, Tetsuya
AU - Christie, Brian R.
AU - Barkho, Basam
AU - McConnell, Michael J.
AU - Nakashima, Kinichi
AU - Lein, Edward S.
AU - Eadie, Brennan D.
AU - Willhoite, Andrew R.
AU - Muotri, Alysson R.
AU - Summers, Robert G.
AU - Chun, Jerold
AU - Lee, Kuo Fen
AU - Gage, Fred H.
PY - 2003/5/27
Y1 - 2003/5/27
N2 - DNA methylation-mediated epigenetic regulation plays critical roles in regulating mammalian gene expression, but its role in normal brain function is not clear. Methyl-CpG binding protein 1 (MBD1), a member of the methylated DNA-binding protein family, has been shown to bind methylated gene promoters and facilitate transcriptional repression in vitro. Here we report the generation and analysis of MBD1-/- mice. MBD1-/- mice had no detectable developmental defects and appeared healthy throughout life. However, we found that MBD1-/- neural stem cells exhibited reduced neuronal differentiation and increased genomic instability. Furthermore, adult MBD1-/- mice had decreased neurogenesis, impaired spatial learning, and a significant reduction in long-term potentiation in the dentate gyrus of the hippocampus. Our findings indicate that DNA methylation is important in maintaining cellular genomic stability and is crucial for normal neural stem cell and brain functions.
AB - DNA methylation-mediated epigenetic regulation plays critical roles in regulating mammalian gene expression, but its role in normal brain function is not clear. Methyl-CpG binding protein 1 (MBD1), a member of the methylated DNA-binding protein family, has been shown to bind methylated gene promoters and facilitate transcriptional repression in vitro. Here we report the generation and analysis of MBD1-/- mice. MBD1-/- mice had no detectable developmental defects and appeared healthy throughout life. However, we found that MBD1-/- neural stem cells exhibited reduced neuronal differentiation and increased genomic instability. Furthermore, adult MBD1-/- mice had decreased neurogenesis, impaired spatial learning, and a significant reduction in long-term potentiation in the dentate gyrus of the hippocampus. Our findings indicate that DNA methylation is important in maintaining cellular genomic stability and is crucial for normal neural stem cell and brain functions.
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U2 - 10.1073/pnas.1131928100
DO - 10.1073/pnas.1131928100
M3 - Article
C2 - 12748381
AN - SCOPUS:0037636512
SN - 0027-8424
VL - 100
SP - 6777
EP - 6782
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 11
ER -